Comparison between effects of ketamine and midazolam as co-induction agents with propofol for prosealTM laryngeal mask insertion

16 © 2016 Latif Mohamed et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4. 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited Comparison between effects of ketamine and midazolam as co-induction agents with propofol for proseal laryngeal mask insertion


Introduction
Managing the airway remains a core and important anaesthetists' skill. 1 Brain et al first introduced the non-invasive supraglottic airway device (SAD) called the laryngeal mask airway TM (LMA) to begin a new era in airway management. 2 It has since become an invaluable template for newer generations of airway devices.A second generation SAD, the ProSeal TM laryngeal mask airway (PLMA) is an improved version which allows higher sealing pressures and oesophageal drainage to prevent gastric aspiration and insufflation. 3 Satisfactory anaesthetic induction conditions are best provided by propofol compared to other intravenous induction agents. 4However, when propofol was used as a single induction agent in unpremedicated patients, doses exceeding 2.5 mg/kg were required to allow smooth and atraumatic LMA insertion. 5Elevated propofol doses are not desirable as the cardiorespiratory depression is dose dependant. 6tamine, an N-methyl d-aspartate (NMDA) receptor antagonist, has beneficial airwaymaintaining and sympathomimetic effects when used as a co-induction agent at sub-anaesthetic Latif Mohamed et al.Sri Lankan Journal of Anaesthesiology: 24(1): 16-21(2016)  doses. 4,7idazolam, a short acting benzodiazepine has been shown to attenuate propofol related cardio-respiratory depressant effects and at the same time reduces the risk for awareness with its anterograde amnesic effects. 8ur study compared the effects of these two drugs as co-induction agents with propofol for PLMA insertion in adults as the literature has thus far, only compared them in children. 9

Materials and Methods
This prospective, randomised, double blind comparative study was conducted following institutional approval.A total of 118 patients with American Society of Anaesthesiologists (ASA) physical status Class I or II, aged between 18 to 60 years old scheduled for elective surgeries requiring PLMA insertion were enrolled.Patients with hyper-reactive airway disease, anticipated difficult airway, body mass index (BMI) > 35 kg/m 2 , gastric aspiration risk, allergy to study drugs and those on regular sedatives, psychiatric medications or β-blockers were excluded.
Explanation about the study and written informed consent was obtained from recruited patients during preoperative assessment.All patients were fasted for 6 hours and no sedative premedication was given.Demographic data including age, weight, height, gender and ASA status were recorded.They were randomly allocated into 2 groups, Group K (Ketamine) and Group M (Midazolam) using computer generated random numbers.One anaesthetic doctor prepared and administered the drugs while another who was blinded to the study drugs, inserted the PLMA and assessed the insertion conditions.Insertion of the PLMA was done by an anaesthetic registrar in-charge of that operating room, having at least 3 years anaesthetic experience and familiar with the introducer technique of PLMA insertion.The study protocol was given and explained to both the anaesthetic doctors involved prior to patient induction.
In the operating theatre, standard monitoring was applied including electrocardiogram (ECG), non-invasive blood pressure (NIBP) and pulse oximetry prior to induction of anaesthesia.The PLMA size, maximum cuff inflation volume and oro-gastric tube size were selected based on the patient's weight. 10All patients were hydrated with 5ml/kg Hartmann's solution via a 20G intravenous cannula.
A maximum of three PLMA insertion attempts were allowed per patient.In between PLMA insertion attempts, the patient's lungs were ventilated for 30 seconds using facemask with 100% oxygen devoid of volatile agents.Anaesthesia was maintained with boluses of i.v.propofol 0.5mg/kg titrated to patients' requirements.If PLMA insertion was unsuccessful, an alternative device such as endotracheal tube was to be used.However, the conditions during PLMA insertion were graded at the first attempt only.The total number of Latif Mohamed et al.Sri Lankan Journal of Anaesthesiology: 24(1): 16-21(2016)  attempts and any additional propofol doses given was recorded.
Patients were allowed to breathe spontaneously after successful PLMA insertion.Assisted manual ventilation was provided when the apnoeic period exceeded 30 seconds from time of PLMA insertion to ensure that the SpO 2 remained > 95%.Manual ventilation was ceased when adequate spontaneous respiration returned.The duration of apnoea was recorded via a digital timer as the time from the end of propofol injection until the return of adequate spontaneous ventilation.Thereafter, anaesthesia was maintained with sevoflurane 2-3% in oxygen(50%):air(50%) mixture until the minimum alveolar concentration (MAC) of 1.0 to 1.3 was achieved.
Non-invasive systolic, diastolic and mean arterial blood pressure (SBP, DBP and MAP respectively), heart rate (HR) and SpO 2 were recorded before induction of anaesthesia (baseline 0 min), and at intervals designated as 1 (study drug bolus administered), 2 (propofol bolus given), 3 (immediately after successful PLMA insertion) and at every one minute thereafter up to 3 minutes following PLMA insertion.Respiratory rate (RR) and ETCO 2 were recorded every minute for 5 minutes following a successful PLMA insertion.
Rescue i.v.ephedrine 6mg boluses were given when >20% reduction of MAP occurred and this was documented.Adverse incidences such as excessive secretions, lacrimation, breathholding, post-operative emergence delirium or sedation were recorded.
Sample size was calculated using the PS Power and Sample Size Calculations program (version 3.0).Based on Goel et al (2008), 51 patients per arm were required to detect more than 20% change in SBP. 9 The power of the study was taken at 80% with a Type I error of 0.05.A total of 118 patients were recruited to include a dropout rate estimated at 15%.All data were analysed by SPSS statistical package programme (Version 22; IBM SPSS Inc Chicago, IL).Differences of numerical data between groups were evaluated using student's t-test.Categorical data were analysed with the Chi-Square test.A p value of <0.05 was regarded as statistically significant.

Results
A total of 118 patients were enrolled and none were excluded from the study as there was no incidence of failed PLMA insertion.There were no statistically significant differences in age, gender, BMI, ASA or types of surgeries between groups.Duration of surgery and anaesthesia were significantly longer in Group K.  * p < 0.05 considered as statistically significant.
The overall insertion condition scores were comparable between groups.Group K and Group M had 89.8% and 94.9% satisfactory ('excellent' and 'good') conditions respectively.One patient in Group K had unacceptable grading.

Discussion
'Co-induction' describes the practice of combining small doses of anaesthetic agents to reduce the overall dose of induction drugs required. 13It allows a balance between therapeutic effects and the unwanted side effects. 14Studies in children showed that 3.5 mg/kg propofol as the sole induction agent was required for good LMA insertion conditions. 4,15o-induction with either ketamine or midazolam further improved the LMA insertion conditions. 4,15 n our study of adult patients, the total propofol dose used in both groups corresponded to an initial induction dose of 2 mg/kg with insignificant additional propofol doses thereafter.The satisfactory PLMA insertion conditions induced by an acceptably lower propofol dose due to co-induction agents reaffirm previous literature findings. 15tamine's additive effects are due to its antagonism on NMDA receptors. 9In our study, both ketamine and midazolam provided comparable overall PLMA insertion conditions when co-induced with propofol.Co-induction with ketamine however, produced better full mouth opening, and hence, effective jaw relaxation.This was similarly reported by Yousef and Elsayed in their study on children. 16 found that co-induction with midazolam produced a significantly longer duration of apnoea compared to ketamine.This suppression of breathing effort is attributed to the synergistic action between midazolam and propofol at the common GABA receptor sites.Although this may have contributed to the high satisfactory scores during PLMA insertion, in practice this marginal time delay of 0.8 minutes was neither a major clinical advantage nor inconvenience.Opioids are known to improve the insertion conditions but with an associated prolonged apnoea duration. 3,6rway manipulation stimulates the autonomic nervous system.Haemodynamic parameters can increase 20% after LMA insertion, with an additional 30% after orotracheal intubation. 1 We did not find any significant blood pressure and HR changes compared to baseline values in both the ketamine or midazolam co-induction groups.However, maintenance of haemodynamic parameters was better with the ketamine group who had significantly higher SBP, DBP, MAP and HR.This was most pronounced at the initiation of propofol bolus injection.The sympathomimetic action of ketamine offsets the sympatholytic effect of propofol leading to less notable haemodynamic reduction thereafter. 9tilising ketamine as a co-induction agent with propofol may be beneficial in unfit or elderly patients who are more susceptible to haemodynamic instability during induction of anaesthesia.
We found minimal and comparable undesired responses between ketamine and midazolam coinduction during PLMA placement.Movement of the head or limbs were the most frequently encountered.Propofol by itself is known to cause involuntary movements. 4Patients who received the ketamine-propofol combination had marginally higher incidence of coughing or gagging, probably due to ketamine's ability to maintain airway reflexes. 9Benzodiazepines on the other hand, are known to reduce upper airway reflexes. 9e main limitation in this study is the fact that a control group of propofol induction used alone was not included.The exclusion was intentional as unwanted haemodynamic instability was anticipated when higher propofol doses are solely used.
In conclusion, both propofol with either ketamine or midazolam as a co-induction agent provided overall comparable PLMA insertion conditions and preservation of baseline haemodynamic parameters.The ketaminepropofol combination had a shorter duration of apnoea, better mouth opening and haemodynamic profile when compared to the midazolam-propofol combination.

Figure 2 :
Figure 2: Comparison of SBP, DBP, MAP and HR at various time intervals.

Table 1 :
Demographic and operative data.

Table 3 :
Conditions during insertion of PLMA.